Multi-epitope vaccine design against leishmaniasis using IFN-γ inducing epitopes from immunodominant gp46 and gp63 proteins.

There is no currently approved human vaccine against leishmaniasis. Utilization of immunogenic antigens and their epitopes capable of enhancing immune responses against leishmaniasis is a crucial step for rational in silico vaccine design. The objective of this study was to generate and evaluate a potential vaccine candidate against leishmaniasis, designed by immunodominant proteins from gp46 and gp63 of Leishmania major, which can stimulate helper T-lymphocytes (HTL) and cytotoxic T-lymphocytes (CTL). For this aim, the IFN-γ-inducing MHC-I and MHC-II binders were predicted for each examined protein (gp46 and gp63) and connected with appropriate linkers, along with an adjuvant (Mycobacterium tuberculosis L7/L12) and a histidine tag. The vaccine's stability, antigenicity, structure, and interaction with the TLR-4 receptor were evaluated in silico. The resulting chimeric vaccine was composed of 344 amino acids and had a molecular weight of 35.64 kDa. Physico-chemical properties indicated that it was thermotolerant, soluble, highly antigenic, and non-allergenic. Predictions of the secondary and tertiary structures were made, and further analyses confirmed that the vaccine construct could interact with the human TLR-4 receptor. Virtual immune simulation demonstrated strong stimulation of T-cell responses, particularly by an increase in IFN-γ, following vaccination. In summary, the in silico data indicated that the vaccine candidate showed high antigenicity in humans. It was also found to trigger significant levels of clearance mechanisms and other components of the cellular immune profile. Nevertheless, further wet experiments are required to properly assess the efficacy of this multi-epitope vaccine candidate against leishmaniasis.

Development of nanocomposites based on chitosan/reduced graphene oxide for wound healing application.

Nanocomposites containing different effective materials have various effects, such as antioxidant, and anti-inflammatory activity, which are desirable for wound dressing. Herein, nanocomposites based on chitosan/reduced graphene oxide (CS/rGO) containing curcumin (CS/rGO/Cur), curcumin and papain (CS/rGO/Cur/Pa), curcumin, papain, and collagen peptide (CS/rGO/CP/Cur/Pa), prepared using ionic gelation method and characterized by Fourier Transform Infrared (FTIR), Differential Light Scattering (DLS), X-ray diffraction (XRD), and Scanning Electron Microscope (SEM). Subsequently, the nanocomposite's potential for wound healing was studied through parameters such as porosity, swelling, degradability, anti-inflammatory, antioxidant, antibacterial, cell viability, and in-vivo. The results of FTIR, XRD, SEM, and DLS showed that the nanocomposites synthesized properly with an almost spherical morphology, an average diameter of below 100 nm (mostly 40-85 nm), and a hydrodynamic diameter of 455-616 nm. The various tests demonstrated the nanocomposite's effectiveness in wound healing. The results showed that CS/rGO/CP/Cur/Pa increased the anti-inflammatory and cell viability up to 99.7 % and 395 %, respectively, which is higher than others. Animal tests on rats showed that CS/rGO/CP/Cur/Pa accelerated the wound healing rate up to 70 %. In conclusion, the results showed that the nanocomposites based on CS/rGO significantly improve wound healing, and the presence of collagen peptides boost their wound healing potency.

Cytopathologic features of epithelioid hemangioendothelioma including touch imprints for rapid on-site evaluation.

Objectives: Epithelioid hemangioendothelioma (EHE) is a vascular tumor of intermediate malignant potential, which presents as infiltrative lesions involving multiple organs. We reviewed our institutional experience with the cytologic diagnosis of this neoplasm including the performance of rapid on-site evaluation (ROSE). Material and Methods: From our institutional database, we identified 29 cytology specimens, obtained between 2012 and 2020, from 21 patients with biopsy confirmation of EHE. ROSE and final diagnosis were compared. All cytology slides were reviewed, and selected cytologic features were recorded. Results: The cohort included 29 specimens comprising 17 (59%) from liver, 6 (21%) from lung, 2 (7%) from lymph node, and 4 (14%) from other sites. At ROSE, 8/27 (30%) were reported inadequate, yet on review, all cases contained scattered cells typical of EHE in the touch imprint air-dried slides including two cases reported with a final diagnosis of non-diagnostic. All cases contained epithelioid and plasmacytoid cells with ovoid nuclei, fine chromatin, delicate (or biphasic) cytoplasm, and scattered cells with delicate, elongated cytoplasmic tails. The majority 26/29 (90%) of cases had multi-nucleated and multi-lobated nuclei. Intracytoplasmic lumens/blister cells were in 17/29 (59%), and a subset had erythrocytes therein (4/29, 14%). Metachromatic fibromyxoid or fibrotic stroma fragments were commonly seen (23/29, 79%). Mitoses and necrosis were absent in all cases. Of 11 tested cases, WWTR1::CAMTA1 and YAP1::TFE3 fusions were detected in nine and two cases, respectively. Conclusion: EHE has distinctive cytologic features which are often under-recognized during ROSE.

Complement C3-α and C3-ß Levels in Synovial Fluid But Not in Blood Correlate With the Severity of Osteoarthritis Research Society International Histopathological Grades in Primary Knee Osteoarthritis.

BACKGROUND: Primary osteoarthritis (OA) is the most common cause of knee arthritis worldwide. The knee synovial fluid complement C3-ß chain levels have been shown to correlate with clinical symptoms of knee OA. It is not known whether the complement C3 in the synovial fluid is derived from the circulation or is produced locally in the knee. METHODS: Fifty primary OA patients undergoing a total knee arthroplasty procedure were evaluated for biochemical analyses of C3-α and C3-ß chains in the synovial fluid and blood plasma. These levels were corelated with the severity of corresponding knee OA based on the Osteoarthritis Research Society International (OARSI) grade. RESULTS: Both synovial C3-α and C3-ß levels correlated significantly with the severity of OA. Neither plasma C3-α levels nor C3-ß levels significantly correlated with OARSI grading. Neither synovial C3-α levels nor C3-ß correlated significantly with plasma C3-α or C3-ß levels, respectively. Synovial C3-α chain and C3-ß chain levels were significantly higher in the grade >6 group. In plasma, neither C3-α chain levels nor C3-ß chain levels were significantly different between the groups. Neither synovial C3-α nor C3-ß levels significantly correlated with plasma erythrocyte sedimentation rate or C-reactive protein levels. CONCLUSION: In knee primary OA, C3 seems to be produced and released locally into the synovial fluid instead of being derived from blood in the circulation. Synovial C3 levels, but not blood plasma C3, correlate with the histopathological severity of primary OA in the knee. Synovial C3 may be an important factor in the pathogenesis of primary OA clinical symptoms and a potential target for therapeutic intervention.

Trophic transfer, bioaccumulation, and health risk assessment of heavy metals in Aras River: case study-Amphipoda- zander - human.

Heavy metals (As, Pb, Cd, and Cu) were traced in a model of the aqueous food chain in the Aras River, located in northwest of Iran. The selected model included the zander (Sander lucioperca L.) and crustacean species known as amphipods (Gammarus sp.) which belong to the food chain of this ray-finned fish. A total of 172 samples (70 fish and 102 amphipods) were collected randomly and analyzed for heavy metals using atomic absorption spectrophotometry (AAS). The results showed that the accumulation of heavy metals in both taxa are in the order of As > Pb > Cd > Cu, and concentrations of heavy metals in fish muscle are higher than Gammarus sp. in all stations in different seasons. Specimens of station (1) displayed the highest heavy metal content due to local industrial activities. The recorded concentrations of As, Pb, and Cd exceed the permissible limits. There is a close correlation between the concentrations of heavy metals in the amphipods and zanders. Target hazard quotient (THQ), total target hazard quotient (TTHQ), and carcinogenic risk (CR) were calculated to assess risks to human health. The average of THQ for As (1.43) exceeded the international standards and presenting health risks to the consumers of this fish species. The TTHQ for heavy metals was estimated higher than 1. At all stations, the value of CRCd > 1 × 10-3 indicating the degree of carcinogenicity of this metal in all parts of the Aras River. Therefore, according to our results, efficient control measures and regular biomonitoring should be established in this region.

Ephrin-A1 and the sheddase ADAM12 are upregulated in COVID-19.

More than 3.5 million people have died globally from COVID-19, yet an effective therapy is not available. It is, therefore, important to understand the signaling pathways that mediate disease progression in order to identify new molecular targets for therapeutic development. Here, we report that the blood serum levels of ephrin-A1 and the sheddase ADAM12 were significantly elevated in COVID-19 patients treated at SUNY Downstate Hospital of Brooklyn, New York. Both ephrin-A1 and ADAM12 are known to be involved in inflammation and regulate endothelial cell permeability, thus providing a gateway to lung injury. The clinical outcome correlated with the ephrin-A1 and ADAM12 serum levels during the first week of hospitalization. In contrast, the serum levels of TNFα were elevated in only a small subset of the patients, and these same patients also had highly elevated levels of the sheddase ADAM17. These data indicate that ephrin-A1-mediated inflammatory signaling may contribute to COVID-19 disease progression more so than TNFα-mediated inflammatory signaling. They also support the notion that, in COVID-19 inflammation, ADAM12 sheds ephrin-A1, while ADAM17 sheds TNFα. Furthermore, the results suggest that elevated serum levels and activity of cytokines, such as TNFα, and other secreted inflammatory molecules, such as ephrin-A1, are not simply due to overexpression, but also to upregulation of sheddases that release them into the blood circulation. Our results identify ephrin-A1, ADAM12, and other molecules in the ephrin-A1 signaling pathway as potential pharmacological targets for treating COVID-19 inflammation.

A Rare Indolent Course of Rhinocerebral Mucormycosis.

Mucormycosis is a highly invasive and rapidly progressing form of fungal infection that can be fatal. The infection usually begins after oral or nasal inhalation of fungal spores and can enter the host through a disrupted mucosa or an extraction wound. The organism becomes pathogenic when the host is in an immunocompromised state. There are several clinical presentations of mucormycosis including rhinocerebral, pulmonary, cutaneous, gastrointestinal, disseminated, and miscellaneous forms. The most common clinical presentation of mucormycosis is the rhinocerebral form which has a high predilection for patients with diabetes and metabolic acidosis. An indolent disease course taking weeks to months of this infection is rare making it difficult to diagnose. Therefore, early detection and prompt treatment with surgical and antifungal therapy are very important in achieving good treatment outcomes.

Administration of high titer convalescent anti-SARS-CoV-2 plasma: From donor selection to monitoring recipient outcomes.

Early in the SARS-CoV-2 pandemic, convalescent plasma (CP) therapy was proposed as a treatment for severely ill patients. We conducted a CP treatment protocol under the Mayo Clinic Extended Access Program at University Hospital Brooklyn (UHB). Potential donors were screened with a lateral flow assay (LFA) for IgM and IgG antibodies against the SARS-CoV-2 S1 receptor-binding domain (RBD). Volunteers that were LFA positive were tested with an ELISA to measure IgG titers against the RBD. Subjects with titers of at least 1:1024 were selected to donate. Most donors with positive LFA had acceptable titers and were eligible to donate. Out of 171 volunteers, only 65 tested positive in the LFA (38.0%), and 55 (32.2%) had titers of at least 1:1024. Before our donation program started, 31 CP units were procured from the New York Blood Center (NYBC). Among the 31 CP units that were obtained from the NYBC, 25 units (80.6%) were positive in the LFA but only 12 units (38.7%) had titers of at least 1:1024. CP was administered to 28 hospitalized COVID-19 patients. Patients who received low titer CP, high titer CP and patients who did not receive CP were followed for 45 days after presentation. Severe adverse events were not associated with CP transfusion. Death was a less frequent outcome for patients that received high titer CP (>1:1024) 38.6% mortality, than patients that received low titer CP (≤1:1024) 77.8% mortality.

An updated checklist of caridean shrimps of the Persian Gulf and Gulf of Oman.

The material of the present checklist has been collected from the Iranian intertidal and shallow subtidal shores of the Persian Gulf and Gulf of Oman from 2015 to 2019, in addition to re-examining all the materials deposited in the Zoological Museum of the University of Tehran. This checklist providing 16 new records for the Persian Gulf and 15 for the Gulf of Oman raised the number of recorded caridean shrimps to 109 and 49 for these gulfs, respectively. However, the actual number of these shrimps are higher than these numbers due to two facts. Firstly, most of the subtidal diverse ecosystems, e.g. coral reefs and seagrass bed have not been seriously investigated taxonomically. Secondly, there are some members of species complexes and probably some new species in the study which need to be carefully treated.

Annotated checklist of the snapping shrimps of the genus Alpheus Fabricius, 1798 (Crustacea: Decapoda: Alpheidae) from the Persian Gulf and Gulf of Oman, Iran.

In the present study, shrimps belonging to the genus Alpheus from the Persian Gulf and Gulf of Oman are documented based on the existing literature and extensive new sampling from 2013 to 2018 along the Iranian coast. A total of 35 species are recorded from the region, of which 40% (14 species) and 60% (21 species) are new records for the Persian Gulf and Gulf of Oman, respectively. Among 19 sampling localities, A. lobidens De Haan, 1849, A. edwardsii (Audouin, 1826) and A. edamensis De Man, 1888 occurred in 14, 13 and 9 localities, respectively. Among the visited habitats, 14 species (40%) were associated with coral or other sessile invertebrates, 13 species (37%) were collected on sandy or rocky substrates, five species (14%) were obtained from muddy substrates, and three species (9%) were found associated with goby fishes. Among Alpheus species, three (10%) were endemic to the Persian Gulf. Most taxa show affinities to both western Indian Ocean and East Indian/West Pacific Oceans.